IOV-4001 for Melanoma and Lung Cancer

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Iovance Biotherapeutics, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Uveal melanoma, Untreated brain metastases, Organ transplant, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing IOV-4001, a modified immune cell treatment, in adults with advanced melanoma or lung cancer. The treatment aims to improve the ability of the patient's own immune cells to attack cancer by disabling a gene that helps cancer hide.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who require systemic steroid therapy at a dose of 10 mg/day prednisone or equivalent. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment IOV-4001 for melanoma and lung cancer?

Research suggests that combining immunotherapy with other treatments, like radiotherapy or chemotherapy, can enhance its effectiveness in treating non-small cell lung cancer. This implies that similar strategies might improve outcomes for patients receiving IOV-4001. ^{1 2 3 4 5}

Research Team

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Eligibility Criteria

Adults with advanced melanoma or non-small-cell lung cancer (NSCLC) that can't be surgically removed. They must have had certain prior treatments, good organ function, and no untreated brain metastases or recent live vaccines. Participants need a measurable lesion for the study and agree to use effective birth control.

Inclusion Criteria

I have melanoma, worsened within 12 weeks after anti-PD-1/PD-L1 treatment, and received BRAF/MEK inhibitors if BRAF positive.

I have at least one tumor that can be surgically removed.

I have received specific treatments based on my group assignment.

Exclusion Criteria

I have not had a live vaccine within the last 28 days.

I have brain metastases that haven't been treated and are causing symptoms.

I have had another type of cancer in the last 3 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of IOV-4001, a genetically modified autologous tumor-infiltrating lymphocytes (TIL) product

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• IOV-4001 (Monoclonal Antibodies)

Trial Overview The trial is testing IOV-4001 infusion's effectiveness and safety in treating unresectable/metastatic melanoma or advanced NSCLC. It will involve adults who meet specific health criteria and have received previous therapies relevant to their cancer stage.

Participant Groups

Group I: Cohort 2 Experimental Treatment 1 Intervention

Participants with Stage III or IV non-small-cell lung cancer

Group II: Cohort 1 Experimental Treatment 1 Intervention

Participants with unresectable or metastatic melanoma

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Findings from Research

In a study of 453 metastatic non-small cell lung cancer patients treated with immunotherapy, those who received radiotherapy (XRT) doses between 30 and 40 Gy showed significantly better overall survival compared to those who did not receive XRT.

Conversely, patients receiving low total doses of XRT (≤ 10 Gy) and certain fraction sizes (4.1-8 Gy) experienced worse outcomes, indicating that the specifics of radiotherapy can greatly influence the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. Onn, A., Gottfried, T., Stemmer, A., et al.[2021]

In a study of 328 patients with KRAS+ non-small cell lung cancer (NSCLC), only 43 received immune checkpoint inhibitors (IO), showing that KRAS mutations do not significantly affect the efficacy of IO therapy.

The median progression-free survival (mPFS) and overall survival (OS) for KRAS+ patients treated with IO were similar to those of non-KRAS patients, suggesting that KRAS status should not be a determining factor in selecting patients for IO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS Mutant Non-small Cell Lung Cancer Patients: A Retrospective Analysis. Gianoncelli, L., Spitaleri, G., Passaro, A., et al.[2020]

In a study of 197 patients with metastatic non-small cell lung cancer (NSCLC) treated with immunotherapy, those with low baseline serum sodium levels (≤ 135 mEq/L) had significantly poorer clinical outcomes, including lower disease control rates and shorter overall survival (2.8 months vs. 11.6 months).

Low baseline serum sodium concentration was independently linked to worse disease control and overall survival, suggesting it could be a potential prognostic marker for patients undergoing immunotherapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy. Fucà, G., Galli, G., Poggi, M., et al.[2022]

PD-1/PD-L1 inhibitors are effective treatments for advanced non-small cell lung cancer (NSCLC), but currently, only a small number of patients can use them as first-line therapy due to strict selection criteria.

Combining PD-1/PD-L1 inhibitors with other treatments like chemotherapy, targeted therapy, or radiotherapy may enhance their effectiveness and allow more newly diagnosed NSCLC patients to benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[First-line Combination Immunotherapy in Advanced Non-small Cell Lung Cancer]. Peng, X., Zhou, Q.[2020]

In a study of 74 patients with metastatic non-small cell lung cancer (NSCLC) enrolled in early phase immunotherapy trials, those who had not previously received immunotherapy had a median overall survival (mOS) of 8.2 months, while those who had progressed on prior immunotherapy had a slightly better mOS of 10.5 months, indicating that prior treatment may not significantly hinder subsequent immunotherapy effectiveness.

Prognostic scores, particularly the Royal Marsden Hospital (RMH) score and the MD Anderson Cancer Center (MDACC) score, were effective in predicting overall survival, with a high ANC/ALC ratio (NLR) indicating poorer outcomes, suggesting that these scores can help identify patients who may not benefit from early phase immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. Maymani, H., Hess, K., Groisberg, R., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. [2021]

2. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS Mutant Non-small Cell Lung Cancer Patients: A Retrospective Analysis. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[First-line Combination Immunotherapy in Advanced Non-small Cell Lung Cancer]. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. [2022]